Local Stent-Based Release of Transforming Growth Factor–β1 Limits Arterial In-Stent Restenosis

Abstract

The long-term success of intra-arterial stenting remains limited by in-stent restenosis (ISR). Transforming growth factor–β1 (TGF–β1) can inhibit smooth muscle cell (SMC) proliferation and migration and convert SMCs into extracellular matrix (ECM)–synthesizing cells. Here, we evaluate the effects of stent-based delivery of TGF-β1 on ISR in a rabbit model. Channeled stents loaded with TGF-β1 or control microspheres were deployed in rabbit aortas. Stented aortas were harvested at 7 and 28 d and evaluated for Ki-67–positive cells, collagenous ECM production, and intima-to-media (I/M) ratio. At 7 d, the TGF-β1 group exhibited fewer Ki-67–positive cells were found for the TGF-β1 group (17.87 ± 2.18 cells per mm2) relative to control (25.07 ± 2.65 cells per mm2, p = 0.04), but increased collagen content (31.4 ± 2.5 percentage area) compared with control (29.3 ± 1.2 percentage area, p = 0.019). The I/M ratio in the TGF-β1 group was reduced by 50% and 9.1% versus control at 7 d (0.13 ± 0.02 vs. 0.26 ± 0.02, p = 0.0001) and 28 d (1.80 ± 0.05 vs. 1.98 ± 0.08, p = 0.0038), respectively. Stent-based controlled release of TGF-β1 limits ISR and is associated with inhibition of SMC proliferation but an increase in ECM production.